Miglitol increases energy expenditure by upregulating uncoupling protein 1 of brown adipose tissue and reduces obesity in dietary-induced obese mice

Abstract

BackgroundMiglitol is an oral anti-diabetic drug that acts by inhibiting carbohydrate absorption in the small intestine. Recent studies have shown that miglitol reduces obesity in humans and rodents. However, its mechanisms have remained unclear. The purpose of this study was to determine whether miglitol generates heat by activating uncoupling protein 1 (UCP1), an enzyme involved in thermogenesis, in brown adipose tissue (BAT) in mice.MethodsFour-week-old male C57BL/6 J mice were fed a high-fat diet alone (HF) or a high fat diet plus miglitol (HFM). Oxygen consumption (VO2) was used to estimate metabolic rate. A thermal imaging camera was used to quantify heat generation from interscapular brown adipose tissue. We analyzed the protein and gene expressions of UCP1 and the expressions of four proteins related to β3-adrenergic signaling in the pathway activating UCP1 (protein kinase A (PKA), hormone-sensitive lipase (HSL), p38 α mitogen-activated protein kinase (p38αMAPK) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α)).ResultsAt 8 weeks, body weight, epididymal and subcutaneous white adipose tissue and the HOMA-R value of the HFM mice were significantly less than those of the HF mice. Food intake was not different between the HF and HFM mice. VO2 and BAT temperature were significantly higher in the HFM mice. Miglitol significantly enhanced the gene and protein expressions of UCP1 and the expressions of proteins related to β3-adrenergic signaling.ConclusionsMiglitol’s anti-obesity effect was attributed to increased energy expenditure by upregulating UCP1 in BAT (i.e., by thermogenesis) and to enhancement of β3-adrenergic signaling in BAT.

Selection of Suitable Reference Genes for Quantitative Real-Time PCR Normalization in Three Types of Rat Adipose Tissue

“…Uncoupling protein 1 ( UCP-1 ), a brown fat-specific gene, is an energy metabolism-related factor that plays a central regulator role in mitochondrial biogenesis and thermogenesis in BAT [23]. In our study, we observed significantly decreased (−59%, p = 0.005) mRNA levels of UCP-1 in obese rats when calculated with the combination of most stable reference genes ( 36B4 and β-actin ).…”

Effects and mechanisms of auricular vagus nerve stimulation on high-fat-diet—induced obese rats

“…NE, via b 3 -adrenoceptor, initiates triacylglycerol breakdown through BAT thermogenesis. The intracellular signal is transmitted via cAMP and protein kinase A, leading to the release from triacylglycerols of fatty acids that are both the acute substrate for thermogenesis and the regulators of the activity of UCP1 [33]. It is noteworthy that continuous stimulation of NE leads to the dramatic downregulation of b3 expression levels [1].…”

Using miglitol at 30 min before meal is effective in hyperinsulinemic hypoglycemia after a total gastrectomy

“…The route and timing of excretion of α-GIs in patients who have undergone gastric resection may affect the efficacy against hypoglycemia. Recently, it has been shown that miglitol enhanced β3-adrenergic signaling in brown adipose tissue [33,34]. These reports raised the possibility that miglitol can modulate the activity of sympathetic nervous system.…”